Penta Screen

Prenatal screening is routinely
offered for NTD, Down syndrome, and trisomy 18 risk assessment. NTD risk
assessment is based on alpha-fetoprotein (AFP) alone, whereas Down syndrome
and trisomy 18 risk assessments are based on multiple marker combinations that
may include maternal age, AFP, human chorionic gonadotropin (hCG),
unconjugated estriol (uE3), and dimeric inhibin A (DIA). In this screening
test, we include an additional marker: hyperglycosylated hCG (h-hCG).

Multiple studies
have demonstrated the utility of h-hCG in Down syndrome screening.1-12 h-hCG
is a hyperglycosylated form of hCG that is produced by cytotrophoblasts during
embryonic implantation and trophoblast invasion of the uterine wall. Levels
tend to be increased in Down syndrome-affected pregnancies. As shown in Table
1, the addition of h-hCG improves screening sensitivity (ie, detection rate).
Based on previous experience,13 the improvement in sensitivity gained from an
additional marker should lead to a lower false-positive rate in clinical
practice. Thus, the number of amniocenteses required for follow-up of
“positive” test results may be reduced.

Women with
values above the cut-off listed in Table 2 are considered at increased risk
of carrying an affected fetus. Inaccurate patient information can
substantially affect risk assessment. Risks can be recalculated using
corrected patient information; call 800-642-4657, ext. 4455.

Normal Risk for NTD

Normal levels do not ensure birth of a normal infant; AFP screening has a
false-negative rate of 8% for anencephaly and 38% for spina bifida.16 Closed
NTD will not be detected in most cases.

Increased Risk for NTD

Ultrasonography is recommended to confirm the
gestational age or detect the presence of twins or anencephaly. When the
gestational age is <19 weeks and an increased AFP MoM of
≥2.5 but <3.5 is
still unexplained, repeat blood sampling and AFP measurement are recommended
to confirm the elevation. Repeat blood sampling is not recommended when 1)
the Down syndrome or trisomy 18 risk is elevated; 2) the AFP MoM is
≥2.5 and
the gestational age is advanced (≥19 weeks); or 3) the AFP MoM is
≥3.5.
Follow-up for abnormal AFP results includes genetic counseling, level II or
III ultrasound examination, and consideration of amniocentesis for
chromosome and AFP analysis. Following these procedures, an unexplained
maternal serum AFP elevation indicates an increased risk for obstetrical
complications, including rupture of membranes and premature labor,
intrauterine growth retardation, and stillbirth.

Increased Risk for Down Syndrome

Obtaining a repeat blood specimen is contraindicated
unless the gestational age was <14 weeks at the time of the first blood
draw. Ultrasonography will provide a more accurate estimation of the
gestational age and may resolve the increased risk. If not, genetic
counseling and cytogenetic analysis of amniotic fluid cells are recommended.
Approximately 2% of pregnancies at increased risk would be expected to have
an affected fetus.

Increased Risk for Trisomy 18

One in
10 pregnancies at increased risk would be expected to have an affected
fetus.15 Genetic counseling and cytogenetic studies of amniotic fluid cells
are recommended.